It has been demonstrated that ischemia-reperfusion injury can be initiated by clonally-specific pathogenic IgM that activates the classical pathway of complement (Zhang et al. (2004) Proc. Natl. Acad. Sci. 101(11):3886-3891). Pathogenic IgM (also referred to as “natural IgM”) recognizes and binds to a self-antigen which is an antigen expressed or exposed on damaged tissue, for example, on damaged ischemic tissue. Binding of pathogenic IgM to the self-antigen initiates inflammation by activating complement in the classical pathway. U.S. Pat. No. 7,442,783 describes the major epitope for binding of natural IgMs as a conserved region within type II non-muscle myosin heavy chain (NMHC) proteins. This epitope is referred to as the N2 12-mer peptide.
Inhibitors of the interaction between the N2 epitope and pathogenic IgM have been described as useful for the treatment of inflammatory diseases and conditions, including ischemia/reperfusion injury. For example, U.S. Pat. No. 8,324,352 describes the murine monoclonal antibody referred to as 21G6. Murine 21G6 (m21G6) was shown to bind to the N2 peptide and provide protection against ischemia/reperfusion injury in animal models. It would be advantageous to develop additional therapeutic agents that bind the N2 peptide and that can be used for treating inflammatory conditions such as ischemia/reperfusion injury.